Phase I and pharmacological studies of pentamethylmelamine administered by 24-hour intravenous infusion.
A Phase I study of pentamethylmelamine (PMM) was conducted, administering the drug as a 24-hr i.v. infusion once weekly for 3 weeks. Doses ranged from 80 to 3000 mg/sq m/week. Twenty-six evaluable patients received a total of 30 courses of PMM. The median performance status of the patients was 60% (range, 40 to 90%), and the median age was 58 years (range, 43 to 72 years). The highest tolerated dose was 2000 mb/sq m/week. Nausea and vomiting were the dose-limiting toxicities; myelosuppression was neither consistent nor severe. One objective response lasting 10 months was noted in a patient with renal cancer. Pharmacokinetic studies using [ring-14C]PMM demonstrated a postinfusion half-life of 14C of approximately 12 hr, with the majority of the radiolabel excreted in the urine. PMM was introduced as a parenteral form of hexamethylmelamine. The present schedule does not permit administration of PMM in a dose greater than the tolerated dose of hexamethylmelamine and does not appear to offer an advantage over the p.o. use of the parent compound.
D000328:Adult; D000368:Aged; D006585:Altretamine / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives / Q000652:urine; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007263:Infusions, Parenteral; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D011379:Prognosis; D014227:Triazines / Q000008:administration & dosage*; D014839:Vomiting / Q000139:chemically induced
D000970:Antineoplastic Agents; D014227:Triazines; D006585:Altretamine; C022048:pentamethylmelamine